Project 1: Epidemiology of and Risk Prediction for Childhood Cancers in the Context of HIV/AIDS in Africa Sub-Saharan Africa (SSA) disproportionately bears the burden of pediatric HIV/AIDS, having approximately 90% of the 1.7 million pediatric cases of HIV. While substantial progress has been made in recent years to limit the number of new cases of HIV among children, there are still an estimated 1.6 million children living with HIV in SSA. These HIV-infected children are at a higher risk for developing cancer as a result of their disease. The epidemiology of HIV-related malignancies among adults has been fairly extensively studied; however, few epidemiologic studies on cancer among children with HIV have been conducted. Our long-term goal is to determine which HIV-infected children are at highest risk of developing a malignancy. To address these gaps in the epidemiology of pediatric HIV-related malignancies in SSA, we propose the following aims: 1. Calculate the prevalence and incidence of cancers among HIV+ children by expanding and updating a cohort of HIV+ children who are treated and followed at the BIPAI Centers of Excellence. We will leverage both the high-quality electronic medical record system in the BIPAI CoE and affiliated clinic network and the large population of HIV-infected children who have been treated at the CoEs since 2004 to understand the distribution of cancers in this high-risk population. Hypotheses: 1) The incidence of certain infection-related cancers will be higher among HIV-infected children age 14 years or younger, and 2) there will be a lower incidence of HIV-associated cancers (e.g., KS) over the timeframe of this cohort compared to historical data, while the incidence of other non-AIDS defining cancers will be higher. 2. Determine the impact of clinical risk factors on pediatric HIV-related malignancy risk in SSA. We will assess the impact of risk factors such as timing of anti-retroviral treatment, HIV stage at cancer diagnosis, severe acute malnutrition at cancer diagnosis, and geoclimatic differences on HIV-related malignancy risk of children living in SSA. We will also assess whether risk of developing HIV-related malignancies is influenced by history of infections and other co-morbidities. Hypothesis: Factors related to a child's HIV infection severity and early life environment underlie risk of developing pediatric HIV-related malignancies in SSA. 3. Identify plasma biomarkers that are more abundant among HIV+ children diagnosed with cancer. Based on evidence from the literature and our own preliminary data, we will compare a standard set of cytokines/chemokines, and markers of virus burden, in 4 groups of children: 1) HIV+/Cancer+, 2) HIV+/Cancer-, 3) HIV-/Cancer+, and 4) HIV-/Cancer-. The goal is to identify biomarkers of cancer risk in HIV+ children that could be utilized with the clinical factors identified in Aim 2 to develop a novel paradigm for cancer screening in this high-risk population. Hypothesis: There are both specific cancer- and HIV-related differences detectable in the plasma of children who develop HIV-related malignancies compared to those who do not.